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Helicobacter pylori

Helicobacter pylori

Dr.B.Boyle

Contents/Aims of

Contents/Aims of

Lecture

Lecture



History



Introduction



Microbiology



Epidemiology and

Transmission



Pathogenesis



Clinical Outcomes of

Infection



Diagnosis



Treatment Options



Future

Objectives: to have a clear understanding of disease caused by

Helicobacter pylori in terms of the above headings

Introduction

Introduction

This discovery have revolutionised the

diagnosis, treatment and prognosis of

upper gastrointestinal disease

H.pylori causes gastritis in over half of the

world`s population and is the aetiological

agent of 95% of duodental ulcers, 70-80%

of gastric ulcers and has casual rate in

probably up to 60-70% of Gastric Cancer

H.pylori -

H.pylori -

Microbiology

Microbiology

Small curved microaerophilic gram-

negative rods 2-4ųm long

Selective medium required for isolation-

10% sheep blood agar + selective

antibiotic supplement

Incubated at 80-85% N

2

, 5-10% CO

2

10% H

2

O @ 37ºC

Identified by urease, oxidase, catalase

Epidemiology

Epidemiology

 Infection occurs worldwide

 Prevalence will depend on the country and population

groups

 Overall prevalence strongly correlates with socio-

economic conditions

 In Middleaged adults in developing countries

prevalence is 80%, in industralised countries 20-50%

( rate of acquistion decreasing)

 Acquisition: Oral Ingestion of the bacterium

 Transmission: Within families in early childhood, not

isolated from water etc, e

Epidemiology

Epidemiology

 H.pylori infection in

adults is usually chronic

without specific therapy:

on the other hand ,

spontaneous elimination

of the bacterium in

childhood is probably

relatively common

 NEJM , Vol. 347, No. 15

Oct 10, 2002

mm.HH

Pathogenesis

Pathogenesis



H. pylori is found only on gastric epithelium

where the organisms tend to cluster around the

junctions between cells and virtually never

penetrate the cells themselves.



H. pylori is able to survive in the gastric

environment which is hostile to growth of most

bacteria.

Figure 2. Pathogen–Host Interactions in the Pathogenesis of

Helicobacter pylori Infection.

Pathogenesis

Pathogenesis

H.pylori Genome

Changes

continuously

Hop Proteins,

Adhesins

Ure 1, p H

Gated urea

channel

Vac A

Vac A Gene

Variants ,

More severe

disease

Bab A adhesin,

Binds fucosylated Lewis B

Blood group antigen

Cag Pathogenicitiy

Island, translocates

CagA into host cell

,phosphorylated ,

Binds SHP-2 TP→

Growthfactor-like

Cellular response and

Cytokine production

by Host cell

Pathogenesis

Pathogenesis

Hop proteins-enzymes which modify the

antigenic structure of surface molecules,

control entry of foreign DNA into bacteria

and influence motility

VacA-95 kd protein, vaculoating cytotoxin

inserts itself into the epithelial cell

membrane and forms a hexameric anion-

selective, voltage dependent channel, in

through which nutrients like HCO

3

and

organic anions can be released and targets

mitochondrial membrane inducing

apoptosis

Figure 2. Pathogen–Host Interactions in the Pathogenesis of

Helicobacter pylori Infection.

Host Response to

Host Response to

H.pylori

H.pylori

 H.pylori causes continuous gastric inflammination in

virtually all infected persons

 Host response triggered by attachment to gastric

epithelium (Class II MHC-apotosis)

 Initially neutrophils then T and B cells,plasma cells and

macrophages

 Role of cag-PAI( Stronger response IL8) and transolation

of Cag A into gastric cells, Urease contributes

 Infected gasric epithelium have increased levels of

interleukin-1ß, interleukin-2,interleukin 6, interleukin-

and TNFà.Interleukin 8 key role

Host Response to

Host Response to

H.pylori

H.pylori

Although the pathogen is extracellular

the T cell response of the gastric mucosa

is Th1 , the resulting cytokines from Th

response (Interleukin 2 and Interferon –

ŷ) promote gastritis( whereas Th

cytokines are protective)

The Th1 response may be due in part to

antral production of Interleukin 18

The Th1 response and Fas mediated

apoptosis may favour survival of the

organism

Gastrin/Somatostatin

Gastrin/Somatostatin

(Duodenal Ulcer ,H.pylori infected )

↠ Hypersecretion Acid

Bacterial products e.g Urea

Inflammatory mediators e.g

Interleukin 1B, TNF)

Histamine relase from Mast cells

6x↑Gastrin Releasing Peptide( mediates release of Gastrin, group of

Peptide hormones produced by antral G cells), more if Cag A +

strain

May be genetic determinant of more response to Gastrin

(if D.U ↑ basal secretion of acid secretion)

Low gastric somatostain level

↑HyperGastrinaemia ↑Pariental cells mass( body)